Current Nutrition Reports (2019) 8:42–51

https://doi.org/10.1007/s13668-019-0257-2

CANCER (MF LEITZMANN, SECTION EDITOR)

The Role of the Microbiome in Cancer Initiation and Progression:

How Microbes and Cancer Cells Utilize Excess Energy and Promote
One Another’s Growth
Corrie M. Whisner 1 & C. Athena Aktipis 2

Published online: 13 February 2019

# The Author(s) 2019

Abstract
Purpose of Review We use an ecological lens to understand how microbes and cancer cells coevolve inside the ecosystems of our
bodies. We describe how microbe-cancer cell interactions contribute to cancer progression, including cooperation between
microbes and cancer cells. We discuss the role of the immune system in preventing this apparent ‘collusion’ and describe how
microbe-cancer cell interactions lead to opportunities and challenges in treating cancer.
Recent Findings Microbiota influence many aspects of our health including our cancer risk. Since both microbes and cancer cells
rely on incoming resources for their survival and replication, excess energy and nutrient input from the host can play a role in
cancer initiation and progression.
Summary Certain microbes enhance cancer cell fitness by promoting proliferation and protecting cancer cells from the immune
system. How diet influences these interactions remains largely unknown but recent evidence suggests a role for nutrients across
the cancer continuum.

Keywords Cancer . Neoplasms . Neoplastic processes . Metastasis . Cell proliferation . Microbiome . Microbiota . Microbe .
Diet . Nutrition . Western diet . Caloric restriction . Immune system . Inflammation . Ecology

Introduction interactions between cancer cells and microbial cells may be

Microbes play an important role in human health and disease,
including influencing our cancer risk. Microbes and cancer cells
coevolve inside the ecosystems of our bodies, and both rely on
incoming resources for their survival and replication. This
means that what we eat—in particular, whether we have excess
energy and nutrients—can affect the growth of both cancer cells
and microbial cells. In addition, cancer cells and microbes can
influence each other’s replication and survival through the pro-
duction of factors. Taken together, these facts suggest that the
This article is part of the Topical Collection on Cancer
* C. Athena Aktipis
aktipis@asu.edu
1
College of Health Solutions, Arizona State University, Phoenix, AZ,
USA
2
Department of Psychology, Center for Social Dynamics and
Complexity, Center for Evolution and Medicine, Biodesign Institute,
Arizona State University, PO Box 871104, Tempe, AZ 85287-1104,
USA
very important in cancer initiation and progression.
The burden of cancer is undeniably high—1,735,350 new-
ly diagnosed cases and 609,640 deaths were estimated for
2018 in the USA alone, and more than 38% of people develop
cancer during their lifetime [1]. With the increasing preva-
lence of cancer comes an increased economic burden with
direct medical costs reaching $80.2 billion in 2015 [2].
These costs will continue to rise as 23.6 million new cases
of cancer are expected by 2030 [2].
Recently, the gut microbiome has emerged as an important
mediating factor of health and disease [3]. We have approxi-
mately as many microbes in and on us as we have human cells
(3.8 × 1013 microbial cells relative to 3.0 × 1013 human cells
[4]). The human gut houses the most diverse and metabolical-
ly varied proportion of these microbes when compared to any
other body surface, serving as home to more than 1000 unique
species. These species express 3.3 million genes—orders of
magnitude more than the 23,000 expressed human genes [5].
Interactions between microbes and human cells play impor-
tant roles in human metabolism including digestion of com-
plex carbohydrates, production of essential amino acids,
Curr Nutr Rep (2019) 8:42–51
creation of beneficial fatty acids and vitamin compounds, and
degradation of xenobiotics including environmental toxins
and medications [6]. During cancer progression, these meta-
bolic interactions between microbes and human cells may
shift from ones that support health to ones that threaten it, as
microbes begin interacting with cancer cells rather than
healthy human cells. Indeed, microbial dysbiosis has been
found to contribute to gastrointestinal cancer development [7].
It is clear that microbes play important roles in obesity,
gastrointestinal, and cardiometabolic disease prevention and
treatment [8], suggesting that microbes alter human metabo-
lism. However, there are still many open questions about how
microbes and cancer cells interact metabolically and how
these processes contribute to cancer. In this review, we evalu-
ate the current literature on microbiota in cancer risk, discuss
how gene-environment interactions contribute to microbial
mechanisms of cancer, explore how diet influences cancer risk
via the microbiome, and describe how cooperative interac-
tions between microbes and cancer cells may influence cancer.
Microbes Contribute to Cancer Risk
The human gut is a diverse ecosystem including fungi, bacte-
ria, viruses, and archaea, of which bacteria from the phyla
Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria
are most prevalent [9]. Microbes can help maintain the intes-
tinal barrier which keeps potentially harmful organisms from
reaching the epithelium where they can cause illness and in-
jury [10]. Currently, microbes are believed to contribute to
cancer risk by modifying DNA in human somatic cells there-
by altering cell cycle controls, accelerating cell proliferation,
and disrupting normal programs for controlled cell death that
protect the body from aberrant cells.
Microbes have been linked to approximately 10–20% of
human cancers [11]. To date, ten microorganisms have been
designated as carcinogens by the International Agency for
Cancer Research, one of which is Helicobacter pylori for its
association with stomach cancer [11]. Despite observed links
to cancer, these microbes reside in a large proportion of the
human population, many of whom never develop cancers as-
sociated with these otherwise commensal microorganisms.
Microbes and Cancer Cells Evolve
in the Ecology of the Body and in the Tumor
Microenvironment
Our bodies are essentially ecosystems in which cells can evolve.
As in any ecosystem, the players that best survive and replicate
end up making up a larger proportion of the next generation in
the population—this is the process of evolution via natural se-
lection. Cancer is fundamentally a problem of cells evolving in
43
the body to proliferate quickly, monopolize resources and evade
cellular controls that otherwise make the body function normally
[12]. Similarly, diseases caused by harmful microbes are the
result of microbes overproliferating, monopolizing metabolic
resources, and producing virulence factors that interfere with
normal organismal functioning [13], thereby allowing further
microbial imbalances (dysbiosis) to occur.
Cancer cells not only evolve inside the ecosystem of the
body, they also can create a microenvironment around the
tumor that facilitates their growth [14, 15]. This tumor-
promoting microenvironment has growth factors, angiogenic
signals (signal growth of blood vessels that feed tumors) and
fibroblast ‘support’ cells [14]. The microenvironment can pro-
mote the tumor, but earlier in progression, it can also be an
important part of limiting the tumor. If tissue homeostasis is
functioning properly and the immune system has not yet be-
come dysregulated, then the microenvironment may help to
suppress cancer [16–18].
More generally, the immune system is an important aspect
of the ecology around tumors. Normally, the immune system
monitors the tissues of the body for pathogens and cancer
cells, targeting harmful cells for destruction. This process of
immune predation helps keep potentially harmful cells from
damaging healthy human tissues. However, cancer cells and
pathogens can also evolve to evade the immune system just
like prey evolves to evade predators [19]. Additionally, other
aspects of the immune response (e.g., inflammation accompa-
nying wound healing) can be co-opted by cancer cells and
pathogens to generate a proinflammatory environment in
which both cancer and pathogen cells can thrive [14, 17].
Tumor microenvironments can include microbes that re-
side in or near the tumor. Microbes can alter the microenvi-
ronment by producing factors that influence cancer cells. For
example, certain strains of E. coli produce colibactin toxin that
is more commonly found in the mucosa of individuals with
colorectal cancer than healthy controls [20]. Colibactin in-
duces cells in the microenvironment to produce growth factors
which may promote tumor growth [21]. Another way that
microbes can influence the microenvironment is through pro-
ducing bacterial biofilms which have been associated with
higher cell proliferation rates and increased risk of colorectal
cancer [22]. The tumor microenvironment in gastrointestinal
tissue can be influenced by all of the microbes and nutrients
that are present. Therefore, what and how much we eat can
have downstream impacts on the ecology of gastrointestinal
tissues in ways that promote or limit cancer.
Excess Energy Can Feed Both Cancer Cells
and Harmful Microbes
Microbial community structure (diversity and abundance of
specific taxa) and function is rapidly influenced by acute [23]
44
and long-term dietary changes [24–26], thereby highlighting
the importance of dietary inputs for gut microbial community
growth and maintenance. Consumption of high-fat or Western
style diets has been associated with cancer [27, 28]. Further,
obesity as a result of excess caloric consumption has been
linked with increased cancer risk [29]. This link between ex-
cess energy consumption and cancer may be mediated by gut
microbial metabolism. Microbiome transfers from obese mu-
rine donors to germ-free counterparts has been shown to lead
to weight gain and fat deposition in recipient mice [30, 31]—
even when mice have the same dietary inputs [30, 32].
The links between cancer and obesity are clear [33], and
some work suggests that microbes may play an important role
in this link. Caloric restriction studies suggest that cancer out-
comes are improved via increased gut microbial diversity and
subsequent reductions in inflammation [34•, 35•, 36, 37]. This
may be mediated by improved gut barrier integrity which
minimizes translocation of microbial-derived inflammatory
markers including lipopolysaccharide and also beneficial
shifts in microbial abundance (e.g., increased abundance of
Lachnospiraceae), as observed in obese women on very low
calorie diets (~ 800 kcal/day) [34•].
As with any ecological system, the introduction of excess
resources can disrupt the normal interactions among the con-
stituents in that ecosystem. In the case of the human body,
introducing excess energy can disrupt the interaction be-
tween the microbes and human somatic cells. Under ideal
conditions, growth and proliferation of microbes and our
somatic cells is limited by access to resources like carbohy-
drates, protein and fat, as well as through somatic cell cycle
controls. Glucose is a preferred fuel source for most human
cells, from which cellular energy in the form of ATP is used
to fuel cellular processes. In the case of cancer, this other-
wise oxygen-requiring pathway switches to less efficient
processes such as fermentation. This metabolic disruption,
referred to as Warburg metabolism [38], results in the pro-
duction of lactate which destroys the extracellular environ-
ment and facilitates invasion into new tissues and metastasis.
Future work should investigate whether these metabolic
shifts also encourage translocation and growth of lactate-
utilizing microbes from the intestinal tract [39] to tumor
regions. Interestingly, there is some evidence that microbes
that thrive in anaerobic conditions may actually suppress
replication of cancer cells, though the mechanisms of action
remain unknown [40].
Dietary Modification Can Influence Microbial
and Cancer Cell Growth
The introduction of agrarian (farmers and pastorals) lifestyles
10,000 years ago followed by the industrial revolution led to
the emergence of a genotype more adept at processing
Curr Nutr Rep (2019) 8:42–51
complex carbohydrates from plant-based foods, rather than
the high-protein diets of hunter-gatherers [41]. Our ancestors
relied on their gut microbes to break down plant fiber so that
their bodies could obtain adequate amounts of energy and
nutrients. Gut microbiota express enzymes that carry out di-
verse reactions, including fermentation, hydrolysis, denitrifi-
cation, sulfate reduction, and aromatic fission, to process com-
pounds that persist in the gastrointestinal tract and are not
metabolized by human enzymes. Today, we have access to
plentiful simple and complex carbohydrates, in addition to
various other foods that our bodies process with little assis-
tance from microbes. This evolutionary mismatch—
especially with regard to increased sugar consumption—
appears to contribute to cancer risk [42].
Fruits, Grains, and Vegetables
Various sugars, starches, dietary fibers, and polyphenolic com-
pounds are present in fruits, grains, and vegetables. Regular
consumption of these plant-based foods has been associated
with cancer prevention [43] (Fig. 1). Many of the plant com-
ponents associated with improved health have been attributed
to the gut microbiota and their ability to metabolize otherwise
non-digestible plant stuffs into bioactive compounds including
short-chain fatty acids and bioactive phytochemicals.
Short-chain fatty acids (acetate, propionate, butyrate) are
byproducts of the fermentation and hydrolysis of complex
carbohydrates and dietary fiber that reach the colonic micro-
biota [44]. Short-chain fatty acid (SCFA) effects begin at the
intestine level, where butyrate is utilized as a primary fuel
source for enterocytes, and extend to systemic influences
where butyrate and propionate regulate glucose and lipid me-
tabolism in the liver [45]. Butyrate also induces cell differen-
tiation, apoptosis, and histone hyperacetylation [46, 47].
While these effects are believed to limit cancer initiation and
progression, the effects of butyrate seem to depend on host
genotype and SCFA concentrations. In a mouse model of co-
lorectal cancer, in which cancer cells preferentially utilized
glucose, butyrate was forced to accumulate in the nucleus
where it ultimately increased histone acetylation and subse-
quent apoptosis thereby decreasing cancer cell proliferation
[48]. Conversely, in mice with mutations in the Msh2 gene,
involved in mismatch repair, microbiota-derived butyrate en-
hanced tumor cell proliferation [49]. Excess production of
acetate in the gut has been linked to altered insulin regulation
and obesity [50], and excess energy production via microbial
conversion of fiber to SCFA may contribute to obesity and
cancer, for which dietary intake is an important mediator
[45, 51].
Consumption of plant polyphenols, flavonoids [52, 53] and
glucosinolates [54, 55], is associated with reduced cancer risk.
Specific microbes can convert glucosinolates from cruciferous
vegetables into isothiocyanates which have anticancer
Curr Nutr Rep (2019) 8:42–51 45

Input (diet) Microbial species Outputs (nutrients, toxins) Effect on human cells

Tight junctions

Provide nutrients
to colon cells
SCFA
Bifidobacteria
longum Limit pathogen
growth
Beneficial

Maintain barrier
function

Lactobacillus
acidophilus Vitamins (eg. biotin, B12) Methylation of DNA
and histone modification

Reduce DNA damage

Antioxidants/Flavonoids
Reduce inflammation
Saccharomyces
boulardii

Glucosinolates Inhibit tumor growth

N-nitroso Base pair shifts

compounds in DNA, and
DNA alkylation

Secondary bile acids Tumor proliferation

Salmonella
enterica

Reduced mucus
production
Harmful

Hydrogen sulfide Breakdown

Escherichia coli intestinal barrier

DNA damage

Inflammation
Fusobacterium ROS, RNS & LPS
nucleatum Leaky junctions

Fig. 1 Important metabolites and associated mechanisms that promote and inhibit the collusion of gut microbes and cancer cells. LPS,
lipopolysaccharide; ROS, reactive oxygen species; RNS, reactive nitrogen species; SCFA, short-chain fatty acids

properties. These microbes include Eggerthella spp., Alistipes
putredinis, Eubacterium hallii, and Phascolarctobacterium
faecium [56], of which Eggerthella and Alistipes also degrade
starch and dietary fibers [57]. Fiber-poor diets, which often
lack polyphenols, enhance microbial pathogenicity and
degrade barrier function via loss of intestinal mucus in animal
models [58•], but how this relates to cancer risk remains
understudied. A recent meta-analysis suggests that flavonoids,
quercetin and apigenin, may reduce the odds of colon cancer
[53]. Soy isoflavones have also been implicated in both
46
anticancer and tumor-promoting pathways [59] which may be
dependent on which downstream metabolites and nutrients are
available to gut microbiota [60].
Protein- and Fat-Containing Foods
Proteins and amino acids can also be metabolized into phe-
nols, indoles, ammonia, amines, sulfur compounds, and other
organic acids [61]. These products are the result of hydrolysis,
deamination, decarboxylation, fermentation and elimination
reactions. Fatty acids and other lipids can also be metabolized
by gut microbes, largely in the conversion of primary to sec-
ondary bile acids. These conversions alter both the gut
microbiome as well as liver signaling [62], and have also been
identified as carcinogenic compounds [63, 64].
High-protein and high-fat diets have been shown to in-
crease the production of potentially carcinogenic branched
chain fatty acids, secondary bile acids, and N-nitroso com-
pounds [65, 66] (Fig. 1). Animal product-rich diets that en-
hance secondary bile acid production promote the presence of
bile-tolerant microbes, while decreasing the abundance of
plant polysaccharide-metabolizing microbes [23]. The lower
the carbohydrate content paired with high-protein diets, the
lower the butyrate production and beneficial Roseburia/
Eubacterium rectale abundance in feces [65]. Reductions in
animal product consumption have also been associated with a
lower risk of colon cancer than increasing consumption of
fiber [67]. Together, these facts suggest that consuming ade-
quate carbohydrates while avoiding excess protein may be a
key to reducing cancer risk.
Microbes Can Promote Cancer
Through Various Mechanisms
Ideally, normal human cells and commensal microbes coop-
erate to keep us healthy: we provide resources for microbes,
microbes metabolize nutrients for us; we provide them with an
environment to live in, they help protect us from invading
pathogens [13]. In cancer, this cooperation between normal
cells and beneficial microbes may break down, resulting in
dysbiosis. In some cases, the cooperation between normal
cells and beneficial microbes may be replaced by cooperation
between cancer cells and harmful microbes.
Both microbes and cancer cells evolve in the body’s eco-
system. Thus, microbes and cancer cells that interact with one
another in ways that increase their proliferation and enhance
their ability to avoid detection by the immune system can
potentially gain an evolutionary advantage over those that
do not interact in mutually beneficial ways. In other words,
selection in the body may sometimes favor microbes and can-
cer cells that cooperate in order to gain an evolutionary advan-
tage over non-cooperators, with cooperation being stabilized
Curr Nutr Rep (2019) 8:42–51
by the evolutionary mechanisms of positive assortment [68]
and/or partner choice [69, 70]. In this section, we describe
several mechanisms by which microbes and cancer cells can
potentially enhance one another’s evolutionary fitness, includ-
ing altering one another’s rates of proliferation and survival.
We also discuss how microbes and cancer cells could come to
have high fitness interdependence [71] if they create and
thrive within similar microenvironments.
Microbes Can Damage Cell DNA, Initiating Cancer
Microbes can produce genotoxins which damage DNA.
For example, colibactin produced by E. coli and
Enterobacteriaceae induces double-strand breaks in host
cell DNA [72]. Microbes also produce free radicals that
damage DNA [73]. B. fragilis produces reactive oxygen
species that can damage host DNA and contribute to
colon cancer [74].
Microbes Can Increase Cancer Cell Proliferation
Helicobacter pylori has been well studied as a bacterial strain
with links to cancer. Initially, H. pylori was found to increase
cell proliferation and induce tumors in Mongolian Gerbils
[75]. Twelve human case-control studies further support this
microbe-cancer link with data suggesting that H. pylori detec-
tion was a strong risk factor (odds ratio of 3.0) for gastric
adenocarcinoma [76]. Interestingly, H. pylori colonizes
stomachs of approximately 50% of the world’s population
but only a minority of these individuals develop gastric cancer
[77]. This may depend on carcinogenic phenotypes of the host
which allow H. pylori to persist and induce cancer prolifera-
tion in the stomach [78••] through virulence factor CagA
which stimulates cell proliferation [79].
Cancer Cells and Microbes Can Provide Growth
Factors for Each Other
Senescent cells (cells no longer dividing) can secrete growth
factors into the nearby cellular environment to further growth
of surrounding epithelial tissues. Bacteria capable of produc-
ing the toxin colibactin may mediate this signaling pathway.
Specifically, E. coli production of colibactin is thought to in-
duce the release of growth factors that promote tumor growth
[21, 80].
Cancer Cells and Microbes May Protect One Another
from the Immune System
Commensal microbes in the gut are involved in complex
interactions with the human immune system. Chronic in-
flammation as a result of bacterial infections with
H. pylori, Campylobacter jejuni, and Chlamydia psittaci
Curr Nutr Rep (2019) 8:42–51
can result in lymphomas that are mediated by overactive
adaptive and i nnate immune signaling [81–83].
Enterotoxigenic B. fragilis has been linked to colon can-
cer in mice via inflammatory pathways that involve Stat3
signaling and increases in IL-17-secreting CD4+ T cells
[84]. Microbes also interfere with the ability of the im-
mune system to detect them through a variety of different
mechanisms, including interfering with natural killer cell
activity [85], which could have an impact on the ability of
the body to detect and respond to cancer cells.
Microbes Can Increase Cancer Risk by Altering
the Intestinal Barrier and Associated Biofilms
The mucosal lining provides protection to the host from in-
vading pathogens and also provides an environment to bene-
ficial microbes that helps to cultivate them. When the mucosal
lining is broken down, as happens with infection by harmful
microbes, this can contribute to a pro-cancer environment
with greater inflammation [86].
Some bacteria excrete polymers that can form the basis
for biofilms. These biofilms create microenvironments for
microbes that provide benefits including protection from
external threats and access to resources/nutrients [87].
Biofilms are sometimes found in the colon, and they are
often associated with colorectal cancer, particularly on the
right side of the colon [22], which is the first portion of
the colon that early-stage feces travel through. Tissues
with biofilms on them have been associated with greater
permeability of the intestinal barrier and greater immune
activation [22].
Microbes Can Induce Host Cell Proliferation
Which Can Expand Microbes’ Ecological Niche
Many microbes can use host cells to expand their ecolog-
ical niches through inducing proliferation of the cells up-
on which they rely. For example, viruses replicate them-
selves after entering the nucleus, integrating with host cell
DNA and inducing cell proliferation. This is the mecha-
nism underlying virally initiated cancers such as HPV
[88]. Bacteria can also expand their ecological niches
through inducing cell proliferation. Fusobacteria does this
by entering the cell and inducing proliferation [89], which
expands the ecological niche for the microbes [85]. This
also has the effect of promoting colorectal cancer.
Microbes that bind to epithelial surfaces then increase
the proliferation rates of the cells they are attached to like
H. pylori does to gastric cells [85]. In these situations,
harmful microbes and cancer cells may have aligned fit-
ness interests. Such fitness interdependence can arise any-
time entities can benefit from one another’s success [71],
as is the case when microbes benefit from the expansion
47
of the cancer cell population because this increases the
ecological niche for microbes.
Microbes Can Prompt Cells to Shift to a More
Metastatic Phenotype
One of the key steps in the transition from a benign neoplasm
to a malignant cancer is the epithelial to mesenchymal transi-
tion (EMT), where cells transform from mostly stationary ep-
ithelial cells to motile mesenchymal cells. A number of mi-
crobes, including Bacteroides fragilis, Fusobacterium
nucleatum, and Enterococcus faecalis have been found to
produce toxins that contribute to EMT, typically through al-
tering the normal adhesion between cells [90].
Microbes Produce Quorum Sensing Molecules That
Can Contribute to Metastasis
Some microbes, including Bacillus sp., E. faecium and
Escherichia coli, produce peptides that act as quorum sensing
molecules (molecules that microbes use to coordinate their
gene expression and behavior) that can contribute to metasta-
sis. These quorum sensing molecules appear to alter host ep-
ithelial growth factors, which activate intracellular signaling
that eventually leads to metastasis [91••].
Microbes Alter Cancer Cell Epigenetics to Enhance
Cancer Cell Proliferation
Microbes are capable of producing metabolites that regu-
late DNA expression. For example, Bifidobacterium spp.
produce folate, a major methyl donor in the pathway that
leads to S-adenosylmethionine, the metabolite that donates
methyls to silence genes. F. nucleatum, frequently enriched
in patients with colorectal cancer, has been correlated with
DNA methylation of genes within the inflamed colonic
mucosa which enhance tumorigenesis [92, 93].
Chromatin remodeling via acetylation and deacetylation
of histones is also an important aspect of DNA expression
regulation. The gut microbiome is thought to play a role in
histone acetylation given that butyrate, a metabolite of gut
microbes including Megasphaera, Roseburia,
Faecalibacterium, Clostridium, etc. [94], is a potent induc-
er of intestinal Treg cell differentiation via histone acety-
lation [95]. Non-coding RNAs (microRNA, small interfer-
ing RNA, and long non-coding RNA) have also been
linked to the gut microbiota and host health. Differential
expression of long non-coding RNAs has been observed in
cells colonized with E. coli [96]. Post-transcriptional mod-
ifications via altered microRNA expression have been not-
ed after infection with Salmonella spp. [97] and
F. nucleatum [98••], of which F. nucleatum is thought to
influence colon cancer via autophagy regulation.
48
Opportunities and Challenges in Treating
Cancer Given Interactions
with the Microbiome
Can We Jump Start the Immune System to Break
up Microbe-Cancer Cell Cooperation?
When the immune system is functioning properly, it limits the
growth and proliferation of harmful microbes and cancer cells.
Microbes and cancer cells may cooperate to create an ecological
niche that allows them to proliferate outside of normal immune
control. So immune therapies targeted at disrupting microbe-
cancer cell interactions may have potential for treatment.
Can Specific Microbes Be Used to Control Cancer Cell
Populations as a Part of Treatment?
Microorganisms, such as Mycobacterium bovis BCG, have
been used in cancer treatments for more than 100 years, in-
cluding the successful treatment of bladder cancer [40].
Additionally, many microbial products have been used in can-
cer treatment, including redox proteins like azurin [40]. The
mechanisms of action appear to be diverse, with some activat-
ing the immune system, others inducing cell death via apopto-
sis and others inhibiting the growth of new blood vessels [40],
thereby depriving tumors of resources. Future work should
investigate the metabolic and ecological interactions between
tumor cells and microbes that underlie this effect in order to
discover new microbes that can be used in cancer treatments.
Can Commensal Microbes Enhance the Effectiveness
of Therapy?
In mice, having intact commensal microbes leads to greater
effectiveness of cancer therapy [99], but other microbes re-
duce the effectiveness of cancer therapy and increase resis-
tance [98••]. The mechanisms underlying these positive and
negative effects on therapy are currently unknown. Future
work exploring these interactions could have therapeutic
potential.
Can Foods Containing Prebiotics and Probiotics Help
Prevent and Treat Cancer?
While a few cases of adverse events in cancer patients taking
probiotics have been published [100], the potential benefits of
pre- and pro-biotics observed in pre-clinical models suggest
that these bioactive food components may decrease cancer
risk by improving intestinal barrier function,
immunomodulation, and metabolic and antiproliferative ef-
fects [101]. However, prospective longitudinal data are ex-
tremely limited in humans. This work is required before mak-
ing clinical recommendations.
Curr Nutr Rep (2019) 8:42–51
Conclusion
Human gut microbiota play an important role in enhancing
and inhibiting cancer initiation and progression. Dietary in-
take is an important way of shaping this community but
inter-individual variability in microbiome community struc-
ture may influence how people respond to different dietary
constituents. Not much is known about how dietary inputs
affect microbe-cancer cell interactions, but it appears that ex-
cess energy inputs may encourage the growth of both cancer
cells and pathogenic microbes. While certain microbes can
enhance cancer cell fitness by promoting proliferation and
protecting cancer cells from the immune system, others may
protect against cancer. Nonetheless, there are many open ques-
tions with regard to how individual differences in habitual
dietary intake, microbial structure and function, and human
genetics contribute. Many exciting opportunities for leverag-
ing this new work on microbe-cancer cell interactions to im-
prove prevention and treatment exist. Future work should fo-
cus on understanding the complex dynamic interactions be-
tween cancer cells and microbes over time both in healthy
individuals and cancer patients.
Compliance with Ethical Standards
Conflict of Interest Corrie M. Whisner has received compensation from
Ardent Mills LLC for service as a consultant and participation on a
Scientific Advisory Board.
C. Athena Aktipis is supported by National Institutes of Health grant
U54 CA217376 (to the Arizona Cancer and Evolution Center); however,
this grant was not used to fund efforts in the preparation of this article.
Human and Animal Rights and Informed Consent This article does not
contain any studies with human or animal subjects performed by any of
the authors.
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give appro-
priate credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
Publisher’s Note Springer Nature remains neutral with regard to juris-
dictional claims in published maps and institutional affiliations.
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